'Cooling' Inflamed Brains in Parkinson's

When cells in the body become unwell or injured, they release proteins that inform the body of their stricken situation. Some of these proteins combine together, forming a multi-protein complex, which activates the release of further signalling proteins. These multi-protein formations are called inflammasomes, and they are responsible for causing inflammation - which is the immune system's response to problems affecting our bodies.

Researchers from the University of Queensland in Brisbane (Australia) have reported that one particular inflammasome, known as NLRP3, appears to be highly active in the brains of people with Parkinson's. Specifically, the investigators found that the resident immune cells in the brain - called microglia cells - had particularly high levels of NLRP3.

The scientists have also identified a molecule called MCC950 which acts as a potent inhibitor of this NLRP3 inflammasome. And they found that by orally treating mice once per day with MCC950, they could prevent the loss of dopamine neurons and improve motor function in multiple models of Parkinson's. The researchers also noted a reduction in the accumulation of the Parkinson's-associated protein alpha synuclein. The researchers are now further investigating the use of this NLRP3 inhibitor with a biotech firm called Inflazome, with the ultimate goal of clinically testing it in people with Parkinson's

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When misfolded, the protein alpha-synuclein becomes toxic to neurons and is a key pathological culprit in Parkinson’s. It is therefore an important target for disease-modification. Immunotherapy in Parkinson's attempts to use immune cells, and specifically the antibodies they generate, to target misfolded alpha-synuclein to inactivate it.

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